Competitive Inhibition

Competitive Inhibition

Uncompetitive Inhibition

Mixed Inhibition

Inhibiting a Carboxypeptidase

• Carboxypeptidases bind peptides and cleave peptide bonds

• Design inhibitor that matches the active site

Inhibiting ACE

• Complementary inhibitors

• Thiols are effective

• First generation motif may be tested

Finding the Best Inhibitor• Synthesize and

test a number of compounds

• Find one with lowest Ki

• Captopril very effective, but side effects

Second Generation Motif

• Make inhibitor that binds to more of enzyme

• Expand to a new subsite

Modern Drug Design

Lisinopril (Merck) Hydroxyphosphinyloxy(Squibb)

Oral availability, metabolic stability, toxicity must be considered